The remarkable sensitivity of the small lymphocyte to the effects of ionizing radiation is well known. This cell is also unusual in that death occurs not only in association with cell division but also during interphase. Studies currently in progress document significant discrepancies in the functional capabilities of defined populations of lymphocytes following exposure to varying amounts of radiation. Thus, despite apparent morphologic homogeneity, bone marrow-dependent lymphocytes appear to be more radiosensitive than thymic-dependent cells. Preliminary evidence, utilizing computer-assisted morphometric analysis of defined populations of cells, suggests that the structural events after irradiation leading to cell death are also different for thymic-dependent vs. bone marrow-derived lymphocytes. Thus, the nucleus of an irradiated bone marrow-dependent lymphocyte exposed to 500 rad becomes edematous, enlarges, develops vacuoles, and eventually undergoes lysis while the comparable thymic-dependent cell becomes slightly smaller with clumped nuclear chromatin and eventually becomes pycnotic. The purpose of this proposal is to enlarge upon these observations and to correlate previously defined events, relating to abnormal function, with altered structure in defined populations of lymphocytes exposed to various doses of ionizing radiation. Populations to be evaluated include: murine thoracic duct lymphocytes; thymic-dependent vs. bone marrow-dependent cells; antibody treated thymic-dependent lymphocytes; thymocytes versus recirculating thymic-dependent small lymphocytes; and suppressor versus non-suppressor thymic-dependent lymphocytes. Parameters to be evaluated include: descriptors and trendal changes as defined by objective sub-visual image analysis of nuclear material; ultrastructural evaluation of subcellular components to include membrane-associated receptor sites; capacity of such lymphocyte populations to respond to defined mitogens in characteristic fashion following irradiation. In addition, particular attention will be paid to morphologic alterations occasioned by exposure to low levels of radiation.